rs1063635

Variant names:

• chr6-31412154-G-A
• rs1063635
• NM_001177519.3:c.821G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31412154-G-A
• chr6-31412154-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001177519.3(MICA):​c.821G>A​(p.Arg274Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 1,609,398 control chromosomes in the GnomAD database, including 177,281 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.54 (23287 hom., cov: 30)
  • Exomes 𝑓: 0.45 (153994 hom.)
• Consequence: MICA NM_001177519.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00400
• Publications: 54 publications found

Genes affected

MICA (HGNC:7090): (MHC class I polypeptide-related sequence A) This gene encodes the highly polymorphic major histocompatability complex class I chain-related protein A. The protein product is expressed on the cell surface, although unlike canonical class I molecules it does not seem to associate with beta-2-microglobulin. It is a ligand for the NKG2-D type II integral membrane protein receptor. The protein functions as a stress-induced antigen that is broadly recognized by intestinal epithelial gamma delta T cells. Variations in this gene have been associated with susceptibility to psoriasis 1 and psoriatic arthritis, and the shedding of MICA-related antibodies and ligands is involved in the progression from monoclonal gammopathy of undetermined significance to multiple myeloma. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ENSG00000288587 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.3832868E-6).
• BP6: Variant 6-31412154-G-A is Benign according to our data. Variant chr6-31412154-G-A is described in ClinVar as Benign. ClinVar VariationId is 403085.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001177519.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICA	NM_001177519.3	MANE Select	c.821G>A	p.Arg274Gln	missense	Exon 4 of 6	NP_001170990.1	Q96QC4
	MICA	NM_001289152.2		c.530G>A	p.Arg177Gln	missense	Exon 4 of 6	NP_001276081.1	A0A024RCL3
	MICA	NM_001289153.2		c.530G>A	p.Arg177Gln	missense	Exon 4 of 6	NP_001276082.1	A0A024RCL3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICA	ENST00000449934.7	TSL:1 MANE Select	c.821G>A	p.Arg274Gln	missense	Exon 4 of 6	ENSP00000413079.1	Q96QC4
	MICA	ENST00000892120.1		c.566G>A	p.Arg189Gln	missense	Exon 3 of 5	ENSP00000562179.1
	MICA	ENST00000616296.4	TSL:5	c.530G>A	p.Arg177Gln	missense	Exon 4 of 6	ENSP00000482382.1	A0A024RCL3

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81559 AN: 151410 Hom.: 23246 Cov.: 30

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.615

GnomAD2 exomes AF: 0.505 AC: 120503 AN: 238752 AF XY: 0.505

Gnomad AFR exome AF: 0.701

Gnomad AMR exome AF: 0.614

Gnomad ASJ exome AF: 0.683

Gnomad EAS exome AF: 0.434

Gnomad FIN exome AF: 0.430

Gnomad NFE exome AF: 0.437

Gnomad OTH exome AF: 0.534

GnomAD4 exome AF: 0.448 AC: 653235 AN: 1457870 Hom.: 153994 Cov.: 79 AF XY: 0.453 AC XY: 328331 AN XY: 725126

African (AFR) AF: 0.712 AC: 23757 AN: 33386

American (AMR) AF: 0.625 AC: 27318 AN: 43696

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 17425 AN: 25904

East Asian (EAS) AF: 0.508 AC: 20115 AN: 39622

South Asian (SAS) AF: 0.578 AC: 49581 AN: 85778

European-Finnish (FIN) AF: 0.430 AC: 22906 AN: 53240

Middle Eastern (MID) AF: 0.687 AC: 3845 AN: 5600

European-Non Finnish (NFE) AF: 0.413 AC: 459105 AN: 1110402

Other (OTH) AF: 0.484 AC: 29183 AN: 60242

GnomAD4 genome AF: 0.539 AC: 81651 AN: 151528 Hom.: 23287 Cov.: 30 AF XY: 0.542 AC XY: 40161 AN XY: 74056

African (AFR) AF: 0.693 AC: 28555 AN: 41204

American (AMR) AF: 0.609 AC: 9236 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2347 AN: 3460

East Asian (EAS) AF: 0.439 AC: 2237 AN: 5094

South Asian (SAS) AF: 0.585 AC: 2812 AN: 4810

European-Finnish (FIN) AF: 0.450 AC: 4758 AN: 10568

Middle Eastern (MID) AF: 0.671 AC: 196 AN: 292

European-Non Finnish (NFE) AF: 0.438 AC: 29749 AN: 67924

Other (OTH) AF: 0.614 AC: 1291 AN: 2102

Alfa AF: 0.509 Hom.: 6162

Bravo AF: 0.558

TwinsUK AF: 0.393 AC: 1458

ALSPAC AF: 0.399 AC: 1538

ExAC AF: 0.501 AC: 60473

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.2
DANN	Benign	0.76
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00096	N
MetaRNN	Benign	0.0000024	T
MetaSVM	Benign	-0.92	T
PhyloP100		0.0040
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.0080
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0090	B
Vest4		0.029
MPC		0.12
ClinPred		0.0032	T
GERP RS		-0.10
gMVP		0.25
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1063635; hg19: chr6-31379931; COSMIC: COSV69826356;